Most of the 2.5 million Americans with epilepsy can live normal lives, as long as they take anticonvulsant medication. But for the 20 percent to 30 percent of patients who prove refractory to medication, daily living is much more problematic. These epilepsy patients are plagued with seizures that cannot be controlled and that occur frequently throughout the day, disrupting life to a potentially debilitating degree. One 4-year-old patient, for example, had more than 100 seizures a day and could not talk or eat.

For patients with frequent seizures that can't be controlled with medication, and those who experience unacceptable side effects, surgery is often indicated. While surgery can permanently stop seizures, this option requires careful deliberation. First, physicians must decide at what point to give up on drug therapy and attempt surgery. Second, the area of the brain generating the seizures must be pinpointed and then excised, removing enough brain tissue to eliminate seizures without damaging critical brain function.

Due to the complex nature of surgical intervention, patients must be treated by highly trained specialists, such as those at CPMC's 5-year-old Comprehensive Epilepsy Center, one of five centers in the greater metropolitan area approved by New York State's Department of Health to offer comprehensive epilepsy treatment.

Dr. Timothy A. Pedley, director of the Comprehensive Epilepsy Center, notes that one of the goals of the center is to increase the number of patients who benefit from surgery by developing better techniques for identifying operable lesions in both adults and children.

One such technique is the selective Wada test, a highly specialized test modified by Dr. John Pile-Spellman, associate professor of neurosurgery and of radiology, and used only at CPMC. After a battery of tests (e.g., EEG, MRI, SPECT, PET) have been used to localize the epileptic brain region, physicians must determine if it is safe to remove that portion of the brain. The Wada test, and now the selective Wada test, can tell physicians whether removing the hippocampus (a location where seizures often originate in adults) would result in destroying a vital function, such as the patient's memory.

The Wada test is a fairly common procedure used to determine the location of language and memory dominance in the brain. With epileptic seizures originating in the temporal lobe, it is important to identify where language and memory reside-the brain of a person with epilepsy may have compensated in ways that make it different from the brain of someone without epilepsy-to avoid removing vital structures.

The Wada test involves inserting a catheter into the internal carotid artery and anesthetizing one side of the brain at a time by injecting a short-acting barbiturate. The physician can then test to see which functions remain intact and which, if any, are lost. For example, if the left side of a patient's brain is anesthetized but the patient can still speak, language ability resides on the right side and the part of the left temporal lobe generating the seizures can be removed without concern for postoperative language ability.

If a patient fails the Wada test, i.e., becomes amnesic when the side of the brain generating the seizures is anesthetized, surgery cannot be performed. "The problem is that the Wada test is relatively crude," says Dr. Thaddeus S. Walczak, assistant professor of neurology and director of the Epilepsy Monitoring Unit, "in that it puts one whole side of the brain to sleep, not just the structure being considered for excision."

The selective Wada test involves catheterizing the small vessels that feed the hippocampus. This requires a great deal of technical skill due to the increased risk of stroke and hemorrhage when catheterizing small intracranial vessels. However, the results can be dramatic. While this test is only necessary in a small subset of patients, for those who benefit it means the difference between living with uncontrolled seizures and being completely seizure-free.

Of five patients who failed the Wada test and then were given the selective Wada test at the Comprehensive Epilepsy Center, three were found to be candidates for surgery after all. Two of the three have undergone surgery and are now seizure-free. The third is awaiting surgery.

The potential drawback of the selective Wada test appears to be the risk of complications, especially stroke. Other medical centers that have tried the test have stopped using it for this reason. Dr. Pile-Spellman, who inserts the catheters in patients at CPMC, has used the test successfully with no complications in any patient.

The selective Wada test provides an important clinical advance in treating adults with epilepsy. The Comprehensive Epilepsy Center also works to develop innovative diagnosis and treatment for the many children referred to the center. Children make up a large number of the center's patients because 20 percent of epilepsy cases develop before age 5.

Dr. Douglas R. Nordli Jr., assistant professor of neurology and of pediatrics and an Irving Clinical Research Scholar, notes that children present challenges different from adults because their seizures do not usually originate in the temporal lobe (70 percent of adult seizures are generated in the temporal lobe). Also, the natural history of seizures is often more unpredictable in children and the manifestations are more variable and subtle compared with adults.

Dr. Nordli received an Irving grant for a research project to find methods to determine early which children with infantile seizures will develop intractable epilepsy, particularly focal epilepsy that will require surgery.

The Comprehensive Epilepsy Center, with a multidisciplinary staff of neurologists, pediatric neurologists, neurosurgeons, neuropsychologists, neuropsychiatrists, nurse clinicians, social workers, and EEG technologists, has operated on more than 120 patients with epilepsy in the past four years. Disabling seizures have stopped in more than 70 percent of the patients, and most of the others have had a substantial decrease in the frequency and severity of their seizures. "This is a remarkable medical development for a condition that many physicians still consider incurable," says Dr. Pedley.